1 Rose Medical Center, Denver, Colorado. 2 Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia. 3 Cerner Corporation, Vienna, Virginia. 4 Present address: Research Triangle Institute, Atlanta, Georgia. *Presented at the 15th International AIDS Conference, Bangkok, July 2004. † The findings and conclusions from this review are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention. ‡ A complete list of these investigators can be found in the Appendix. AIDS PATIENT CARE and STDs Volume 20, Number 4, 2006 © Mary Ann Liebert, Inc. Short-Term Safety and Tolerability of Didanosine Combined with High- versus Low-Dose Tenofovir Disproxil Fumarate in Ambulatory HIV-1–Infected Persons* ,† BENJAMIN YOUNG, M.D., Ph.D., 1 PAUL J. WEIDLE, PharmD., M.P.H., 2 ROSE K. BAKER, M.S., M.S. Hyg., 3 CARL ARMON, M.S.P.H., 3 KATHLEEN C. WOOD, B.S.N., 3 ANNE C. MOORMAN, B.S.N., M.P.H., 2 SCOTT D. HOLMBERG, M.D., M.P.H., 2,4 and the HIV OUTPATIENT STUDY (HOPS) INVESTIGATORS ‡ ABSTRACT Coadministration of didanosine (ddI) and tenofovir (TDF) results in increased ddI serum con- centrations, which may lead to increased risk of ddI-associated toxicities. To evaluate the safety and tolerability of ddI/TDF, we performed a retrospective cohort analysis of patients seen in the HIV Outpatient Study, an ongoing dynamic cohort study of HIV-infected persons in clinical care. Study subjects were those who received at least 14 days of combined ddI/TDF before October 2003. Of 260 subjects who received ddI/TDF-based antiretroviral therapy, 155 (60%) received high-dose ddI (400 mg daily dose) and 105 (40%) received low-dose ddI (100–250 mg daily). Forty-two of the high-dose ddI recipients were later switched to low-dose ddI. The median time of observation for those on high-dose ddI only was 5 months, high-dose ddI switched to low-dose ddI was 16 months, and low-dose ddI only was 5 months (p  0.05). Dis- continuations because of toxicity were more frequent on high-dose ddI regimens (34/155, 22%) than on low-dose ddI regimens (9/105, 9%) (unadjusted odds ratio [OR unadj ] 3.0, 95% confi- dence interval [95% CI] 1.30–7.09; p  0.007). Among subjects without preexisting peripheral neuropathy, 12 (12%) of 101 subjects ever on high-dose ddI regimens had treatment-emergent peripheral neuropathy compared to 2 (4%) of 55 subjects on low-dose ddI regimens (OR unadj 3.57; 95% CI, 0.72–24.1; p  0.14). Among patients without a history of pancreatitis, 6 (4%) of 153 subjects developed pancreatitis after starting high-dose ddI regimens, compared to none of the 103 subjects on low-dose ddI regimens (OR adj and 95% CIs undefined; p  0.08). Se- vere laboratory abnormalities of creatinine, phosphorous, and bicarbonate were not different between the groups. A summary variable for any event—discontinuation for toxicity, treat- ment-emergent adverse event or abnormal laboratory values—indicated that 44 (28%) of 155 238